This program is a continuation of an ongoing collaboration between investigators at Massachusetts General Hospital, King's College, and Massachusetts Institute of Technology. The long term objective of this work is to develop a new method of high resolution intravascular imaging to overcome current limitations in cardiac diagnostics, principally the identification of coronary lesions likely to undergo rupture. Most myocardial infarctions (MIs) result from the rupture of small rather than large plaques in the coronary arteries. These plaques contain a relatively large amount of lipid and have thin intimal caps. When these plaques rupture, they release thrombogenic material into the blood, clot forms, and the vessel occludes. These small plaques are beyond the detection limit of any currently available imaging modality. Therefore, a true clinical need exists for an imaging technology capable of identifying these lesions prior to rupture. Optical coherence tomography (OCT), a new method of high resolution imaging, has demonstrated great potential for the assessment of high-risk plaque. OCT is analogous to ultrasound, measuring the intensity of infrared light rather than sound. Its resolution is currently up to 25X higher than high frequency ultrasound (30MHz), the current clinical technology with the highest resolution. Advantages of OCT, in addition to its resolution, are its compact portable design, small catheter diameter, and near real time imaging rate. The general hypothesis of this work is that several advances could substantially improve the ability of OCT to characterize unstable plaque and improve patient risk stratification. These advances include improving penetration, combining OCT with spectroscopy, and processing data for superior interpretation. Each specific aim will address an independent hypothesis that improves the diagnostic capabilities of OCT. The specific aims are: (Aim 1) To Increasing the Penetration through Blood with Index Matching, (Aim 2) To Characterize Tissue with Absorption and Polarization Spectroscopy, (Aim 3) To Reduce Multiple Scattering with Ultrasound, and (Aim 4) To Improve Data Interpretation through Image Processing.